Tuesday, December 7, 2021
Mitochondrial Health

Theresa Lüth – Uncovering the impact of mtDNA methylation in Parkinson’s disease

Parkinson’s disease (PD) is the fastest growing neurological condition with more than seven million affected people worldwide. Disease onset is characterised by tremor, bradykinesia (slowness of movement), and rigidity; symptoms caused by cell death in dopaminergic neurons. Mitochondrial DNA (mtDNA) dysfunction and impairment of mtDNA maintenance have been implicated in the disease. The potential relevance of mtDNA methylation in these processes has been confounded through the methodological limitations of the traditional short-read sequencing technology used in such studies. In order to resolve these questions, Theresa Lüth (University of Lübeck, Germany) sequenced whole-cell DNA derived from blood and iPSC midbrain neurons using the MinION and GridION devices. The direct detection of methylated bases provided by nanopore sequencing revealed lower mtDNA CpG methylation levels in PD samples compared to healthy controls, at statistically significant levels. Confirming CpG methylation in PD pathogenesis in this study, albeit with a small sample size, underscores the importance of methylation profile analysis in future PD and neurodegenerative disease research.

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